The present invention relates to a DNA which, with distinct nucleotide sequence, shows complementarity to human interferon-.gamma. (referred to as IFN-.gamma. hereinafter) messenger RNA (referred to as mRNA hereinafter) and a recombinant plasmid containing the DNA. The DNA also codes for biologically active IFN-.gamma.. The present invention also pertains to a microorganism containing the recombinant plasmid.
Interferons (referred to as INFs hereinafter) are proteins (some of which are in glycosylated form) with antiviral activity, discovered originally by Isaacs and Lindenmann in 1957. It is known that at least three types of IFN, namely IFN-.alpha., IFN-.beta., IFN-.gamma., are produced. Subsequent studies have indicated antitumor activity of the substances in addition to antiviral activity and hence a wide clinical application of these substances is expected. For instance, it has been reported that IFN may be effective against various viral diseases and malignant tumors.
However, because of its species-specificity, only the IFN of human origin can be applied to human beings. The use of the IFN has been quite limited because of difficulties in mass production. Only recently, recombinant DNA technology has been applied to the production of human IFN-.alpha. and IFN-.beta. by microorganisms such as Escherichia coli and Saccharomyces cerevisiae. For the same reasons, development of technology to produce human IFN-.gamma. is also in demand.
To this end, a novel DNA and recombinant plasmid have been developed for producing human IFN-.gamma. with ease and in large quantities.
It has been reported that IFN-.gamma. may have more potent antitumor activity compared to other IFNs [Proc. Natl. Acad. Sci., USA, 77, 5928-5932 (1980)]. Recently, cloning and expression of an IFN-.gamma. cDNA in Escherichia coli as well as the nucleotide sequence of the cDNA have been reported by Gray et al., Nature, 295, 503 (1982).
However, possibility for the presence of IFN-.gamma. cDNA sequence which differs from the sequence reported by Gray et al., could not be ruled out. If present, the IFN protein coded for by such cDNA could manifest different biological activities and may be of great use for clinical application.